Molecular mechanisms and regulation of mitophagy in Saccharomyces cerevisiae

• Applicant: Professor Dr. Andreas Reichert
• Subject Area: Biochemistry ; Cell Biology
• Term: from 2009 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 139534350

Mitochondria, besides their essential function in ATP production, are central players in apoptosis, ageing, and contribute to numerous human disorders. They often exist as a tubular network that is maintained by a balance of fusion and fission events. Genetic defects impairing fusion or fission of mitochondria are causative to certain neuropathies in humans. My group recently identified and characterized in both yeast and mammalian cells a molecular mechanism that links the functional state of mitochondria to their morphology. In both types of model organisms mitochondrial dysfunction leads to the spacial separation of damaged mitochondria from the intact network. Minimizing mitochondrial dysfunction is likely to be of high relevance in counteracting the development of certain human disorders. However, very little is known how dysfunctional mitochondria are removed within cells, and how this contributes to human diseases and ageing. Is this process specifically regulated, what are the signals, and what are the molecular mechanisms involved? Here, I propose to decipher the molecular mechanisms governing the quality control of mitochondria. For this two model organisms will be employed, namely backer’s yeast as well as cultured mammalian cells. One focus will be to test whether dynamic changes of mitochondrial morphology serve as a prerequisite for the removal of dysfunctional mitochondria by an autophagic process termed mitophagy. This may be of particular importance in post-mitotic tissues such as neurons and muscle cells which are the tissues most severely affected in mitochondrial diseases.

• DFG Programme: Research Grants